Cardiovascular and cerebrovascular diseases including coronary artery disease (CAD), peripheral artery disease (PAD), heart attack, ischemic stroke, and transient ischemic attack (TIA), are the number one cause of mortality in the Western world and have a common underlying pathogenic mechanism, atherosclerosis. Atherosclerosis is a slow progressive hardening and narrowing of the arteries caused by buildup of plaque which ultimately restricts blood flow to vital organs. When a plaque becomes unstable and breaks away from the artery wall, it can cause a blood clot that partially or totally blocks blood flow, resulting in oxygen starvation and potentially death. The magnitude of the population affected by atherosclerosis and the socioeconomic costs associated with various manifestations of the disease necessitates the development of an effective treatment. A consensus has emerged that inflammation plays a decisive role in the development and progression of atherosclerosis, and, as such, represents a new potential therapeutic target. To this end, we have developed an apolipoprotein E (apoE) mimetic anti-inflammatory peptide, COG133, which significantly inhibits release of inflammatory cytokines and inflammatory free radicals from macrophages and/or microglia. These reports indicate that COG133 exhibits anti-inflammatory activity in a number of in vitro and in vivo paradigms, and therefore, possesses many of the properties necessary for a therapy for atherosclerosis. Specific Aim 1: Use the apoE-KO mouse model of atherosclerosis to test the hypothesis that COG133 will modulate the following: A) cytokine levels in serum: IL-2, IL-4, IL-5, IL-10, IL-12, GM-CSF, IFN-gamma, TNF-alpha, IL-6 and IL-8 B) lipoprotein levels in serum: total plasma cholesterol and triglycerides as well as amounts of plasma VLDL, LDL, HDL and their respective subclasses in serum of apoE-KO mice treated with COG133 C) volume of plaque in thoraco-abdominal aorta The outcome of these Phase 1 studies will permit a preliminary evaluation of the feasibility of employing COG133 as a novel anti-atherogenic agent that can inhibit and/or prevent the immune dysfunction underlying atherosclerosis. The overall goal of Cognosci Inc. is to develop a novel therapy for atherosclerosis.